| pubmed-article:19564421 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C0169665 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C0001455 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C1412535 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C0040649 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C1332737 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C1705523 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C0332162 | lld:lifeskim |
| pubmed-article:19564421 | lifeskim:mentions | umls-concept:C2926735 | lld:lifeskim |
| pubmed-article:19564421 | pubmed:issue | 18 | lld:pubmed |
| pubmed-article:19564421 | pubmed:dateCreated | 2009-8-27 | lld:pubmed |
| pubmed-article:19564421 | pubmed:abstractText | In noradrenergic progenitors, Phox2a mediates cell cycle exit and neuronal differentiation by inducing p27(Kip1) transcription in response to activation of the cyclic AMP (cAMP) pathway. The mechanism of cAMP-mediated activation of Phox2a is unknown. We identified a cluster of phosphoserine-proline sites in Phox2a by mass spectrometry. Ser206 appeared to be the most prominent phosphorylation site. A phospho-Ser206 Phox2a antibody detected dephosphorylation of Phox2a that was dependent on activation of the cAMP pathway, which occurred prior to neuronal differentiation of noradrenergic CAD cells. Employing serine-to-alanine and serine-to-aspartic acid Phox2a substitution mutants expressed in inducible CAD cell lines, we demonstrated that the transcriptional activity of Phox2a is regulated by two sequential cAMP-dependent events: first, cAMP signaling promotes dephosphorylation of Phox2a in at least one site, Ser206, thereby allowing Phox2a to bind DNA and initiate p27(Kip1) transcription; second, following dephosphorylation of the phosphoserine cluster (Ser202 and Ser208), Phox2a becomes phosphorylated by protein kinase A (PKA) on Ser153, which prevents association of Phox2a with DNA and terminates p27(Kip1) transcription. This represents a novel mechanism by which the same stimulus, cAMP signaling, first activates Phox2a by dephosphorylation of Ser206 and then, after a built-in delay, inactivates Phox2a via PKA-dependent phosphorylation of Ser153, thereby modulating onset and duration of p27(Kip1) transcription. | lld:pubmed |
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| pubmed-article:19564421 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19564421 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19564421 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19564421 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19564421 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:19564421 | pubmed:issn | 1098-5549 | lld:pubmed |
| pubmed-article:19564421 | pubmed:author | pubmed-author:HallMark CMC | lld:pubmed |
| pubmed-article:19564421 | pubmed:author | pubmed-author:WangWen-Horng... | lld:pubmed |
| pubmed-article:19564421 | pubmed:author | pubmed-author:AndrisaniOura... | lld:pubmed |
| pubmed-article:19564421 | pubmed:author | pubmed-author:ShinMin HwaMH | lld:pubmed |
| pubmed-article:19564421 | pubmed:author | pubmed-author:MavilaNirmala... | lld:pubmed |
| pubmed-article:19564421 | pubmed:author | pubmed-author:Vega... | lld:pubmed |
| pubmed-article:19564421 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19564421 | pubmed:volume | 29 | lld:pubmed |
| pubmed-article:19564421 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19564421 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19564421 | pubmed:pagination | 4878-90 | lld:pubmed |
| pubmed-article:19564421 | pubmed:dateRevised | 2010-9-24 | lld:pubmed |
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